P912: ADDING REFRACTORINESS STATUS TO LINES OF THERAPY BETTER DEFINE PROGNOSIS OF A REAL LIFE ITALIAN MULTIPLE MYELOMA POPULATION
Authors: Sonia More’, Laura Corvatta, Valentina Maria Manieri, Erika Morsia, Attilio Olivieri, Massimo Offidani
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Multiple Myeloma (MM) natural history is characterized by serial relapses requiring several lines of therapy (LOTs), driving to a rising refractoriness status which confers poorer outcome as the disease progresses forward. Therapies are approved by regulatory agencies based on prior LOTs according to results of randomized clinical trials testing novel drugs with this modality. Furthermore, recent data showed that outcomes of refractory patients, particularly those double- and triple-refractory, are very dismal (Gandhi et al, Leukemia 2019; Mateos et al, Leukemia 2022), even when such a state is acquired quickly due to earlier use of novel agents Aims: The aim of this study is to separately observe outcomes by LOTs and by refractoriness status (RS), in the same real life MM population and to define the role of RS in predicting outcomes’ within subsequent LOTs. Methods: Data of this study were extracted from our database including 419 MM patients treated in our tertiary centre from 2010 to 2021. Median age was 69 years (range 30–93), PS ≥ 2, R-ISS II/III and renal failure were detected in 22%, 72% and 18% of patients, respectively. Median follow-up was 50 months (range 6–132 months). We retrospectively analysed all courses of therapy, defined as each time a specific LOT has been administered. The 783 different courses of LOT identified from LOT-1 to LOT-5 were subsequently stratified for RS defined as either no refractoriness, < triple-refractoriness or ≥ triple refractoriness to explore its prognostic ability to predict PFS and OS. RS to the anti-myeloma agents was defined as per IMWG criteria. Results: Out of 783 identified courses, 419 regarded LOT-1, 200 LOT-2, 93 LOT-3 and 71 LOT ≥ 4. Old therapies (chemotherapy, thalidomide-, bortezomib- or steroid-based) were administered in 65%, 20%, 7% and 8% from LOT-1 to LOT≥4, new therapies (carfilzomib-, ixazomib-, lenalidomide-, pomalidomide-, venetoclax-, selinexor-based) in 41%, 31%, 18% and 10% from LOT-1 to LOT≥4, and anti-CD38-based therapies were given in 40%, 35%, 16% and 9% in these groups. After LOT-1, no refractoriness was documented in 83% of courses, < triple refractoriness in 36% and ≥ triple-refractoriness in 4% of them. After LOT-2, 16%, 34% and 20% of courses were characterized by no refractoriness, < triple refractoriness and ≥ triple-refractoriness, respectively; after LOT-3 these values were 1%, 17% and 40%, respectively and in LOT ≥ 4 they were 0, 13% and 36%, respectively. Considering subsequent LOT courses, median PFS was 41, 18.5, 10 and 4 months from LOT-1 to LOT ≥ 4, respectively (p<0.001) whereas median OS was 80, 36, 23.5 and 12 months, respectively (p<0.001). Stratifying LOT courses by RS, in those receiving LOT-2 median PFS was 19.5 months if < triple-refractory vs 13 months if > triple-refractory (p=0.01), in LOT-3 and LOT ≥ 4, these values were 11 months vs 7 months (p=0.037) and 6 months vs 3 months (p=0.085), respectively. Median OS in < triple-refractory was 36.5, 23.5, 14.5 months in LOT2, LOT3 and LOT ≥ 4, whereas it was 18, 12 and 4 months in ≥ triple-refractory (p= 0.03, 0.04, 0.05, respectively). Summary/Conclusion: As already known, PFS and OS progressively decreased LOT by LOT. Nevertheless, RS segregated groups of patients with significantly different PFS and, particularly, OS demonstrating a higher prognostic power compared to number of LOTs. This finding could have relevant implications in designing future clinical trials.Keywords: Myeloma, Refractory